This study first systematically evaluated the strong correlation between CD8+ nTIL density in necrotic tumor regions and event-free survival (EFS) in NSCLC patients receiving neoadjuvant PD-1 blockade combined with chemotherapy. The research demonstrates that CD8+ nTIL density exhibits superior predictive accuracy compared to traditional imaging and pathological response assessments, showing independent prognostic value and offering a more precise biomarker for treatment decision-making.
Literature Overview
The article titled 'CD8+ TILs in necrotic tumors after neoadjuvant immunochemotherapy predict outcomes in non-small-cell lung cancer patients', published in Signal Transduction and Targeted Therapy, reviews and summarizes predictive factors for therapeutic outcomes in NSCLC patients undergoing neoadjuvant PD-1 blockade combined with chemotherapy. The study reveals that CD8+ tumor-infiltrating lymphocyte (nTIL) density in necrotic regions significantly correlates with patient prognosis, independent of PD-L1 expression or lymph node metastasis status, highlighting its potential as an independent prognostic biomarker.
Background Knowledge
Non-small-cell lung cancer (NSCLC) represents the most common lung cancer subtype, where surgical resection remains the treatment of choice for early-stage patients despite high postoperative recurrence rates. Recent advancements in neoadjuvant immunochemotherapy have shown promising pathological response rates, particularly major pathological response (MPR) and complete pathological response (pCR). However, reliance on MPR or pCR alone fails to effectively stratify patient prognosis, as some MPR cases still experience early recurrence, necessitating more precise biomarkers for therapeutic evaluation. Tumor necrosis is a common histopathological phenomenon typically associated with tumor aggressiveness. Post-immunotherapy, necrotic regions may retain T-cell-specific tumor antigens, enabling immunohistochemistry (IHC) detection of tumor-infiltrating lymphocytes (TILs), particularly CD8+ T cells. These nTILs likely reflect the immune system's tumor-clearing capacity, serving as a novel indicator for treatment response prediction. This study aims to evaluate the prognostic value of CD8+ nTIL density in NSCLC neoadjuvant therapy and compare its predictive performance against conventional imaging and pathological response criteria.
Research Methods and Experiments
This study conducted retrospective analyses on data from 200 NSCLC patients who underwent neoadjuvant PD-1 blockade combined with chemotherapy, with 99 cases presenting necrotic tumor regions suitable for nTIL density assessment. All samples were collected from three medical centers, utilizing immunohistochemistry (IHC) to measure CD3 and CD8+ TIL densities. Clinical follow-up data were integrated for statistical analysis. The research team employed Kaplan-Meier methods and univariate Cox proportional hazards models to evaluate associations between event-free survival (EFS) and nTIL density, while receiver operating characteristic (ROC) curve analyses were performed to assess predictive performance.
Key Conclusions and Perspectives
Research Significance and Prospects
This study represents the first systematic evaluation of CD8+ nTIL density as a prognostic biomarker in NSCLC patients following neoadjuvant immunotherapy, demonstrating its potential for clinical decision-making. Future research should validate this biomarker's stability in larger cohorts and explore its applicability across other solid tumors. Development of standardized nTIL assessment tools (e.g., machine learning-based software) could enhance clinical implementation efficiency. These findings provide novel biomarkers for evaluating neoadjuvant immunotherapy efficacy and establish theoretical foundations for optimizing postoperative adjuvant treatment strategies.
Conclusion
This study identifies CD8+ TIL density in necrotic tumor regions (nTIL) as a robust predictor of event-free survival (EFS) in NSCLC patients after neoadjuvant immunotherapy. Compared with traditional imaging and pathological response assessments, CD8+ nTIL density demonstrates superior predictive accuracy and stability, unaffected by PD-L1 expression or lymph node metastasis status. The findings highlight the immune activity within necrotic regions as a critical determinant of long-term prognosis, providing a novel biomarker for personalized NSCLC treatment evaluation. These results not only advance optimization of neoadjuvant immunotherapy response evaluation systems but also offer theoretical foundations for future clinical trial designs.
